NADP (nicotinamide adenine dinucleotide phosphate) has been used as a diagnostic reagent for enzymatically analyzing blood and urine [1]. Reactions for transferring phosphates to NAD+ (nicotinamide adenine dinucleotide) have been previously performed by enzymatic synthesis reactions using NAD+; kinases, which are often derived from microorganisms. For example, NAD+ kinases from microorganisms, such as Brevibacteria and Corynebacteria as well as from yeasts and animals and plants are described in “Enzyme Handbook” 1983, Asakura Publishing, p. 339 [20]; and Matsushita H et al. 1986, Can. J. Microbiol. 32:585-590 [2].
NAD+ kinases are classified into the following three main categories according to the type of phosphate donor to NAD+. The relation with industrial utility is summarized in the table below.
TABLE 1Substrate specificityUtility for NAD+Typeof the phosphate donorsynthesis1ATPx (ATP is very expensive)2Both polyphosphate and AT∘3Polyphosphate∘
At present, industrial production of NADP relies on enzymatic processes including ATP-dependent NAD kinases (EC2.7.1.23) catalyzing phosphorylation of NAD in the presence of ATP [2]. This is partially because most of NAD+ kinases are ATP-dependent NAD+ kinases (type 1 in the table above) which are widely present in microorganisms, yeasts, animals and plants so that they are readily available for industrial applications. NADP+ synthesis using ATP-dependent NAD+ kinases must be coupled to ATP regeneration reaction because industrially expensive ATP is used. The balance between ATP regeneration reaction and NADP+ synthesis reaction is summarized by the formulae below.
                                                NAD        +                    +              ATP              →                      NADP        +                    +              ADP                                              ADP              +                      X        -        P                    →              ATP              +              X                  =                      NAD        +                    +                      X        -        P                    →                      NADP        +                    +              X      
X-P: a high energy phosphate compound in living bodies, e.g. acetyl phosphate, carbamyl phosphate, phosphoenol pyruvate, ADP, etc.
X: acetic acid, carbamic acid, pyruvic acid, AMP, etc.
Enzymes used for ATP regeneration reaction: acetate kinase, carbamate kinase, pyruvate kinase, adenylate kinase, etc.
However, the above processes have such disadvantage as expensive ATP and low stability and cellular contents of the enzymes. Thus, NAD+ kinases capable of utilizing inexpensively available polyphosphates as phosphate donors are desirable for industrially producing NADP+ from NAD+. Polyphosphates are polymers of inorganic orthophosphate residues linked via inorganic phosphate bonds energetically equivalent to the phosphate bonds of ATP (FIG. 1) [6]. Polyphosphates are commercially available in larger amounts at very lower cost as compared with ATP.
Polyphosphate-dependent NAD kinases (types 2 and 3 in Table 1) have already been reported by Murata K. et al. (Biotechnol. Bioeng., 1979 21:887-895; and Agric. Biol. Chem., 1980 44:61-68) [4], but they have not been industrially applied because of the low cellular contents thereof in the reported Brevibacterium. This may be attributed to the low activity of polyphosphate NAD kinases in cells of B. ammoniagenes. 
On the other hand, Kawai et al. (Biochem, Biophys. Res. Commun., 276, pp. 57-63 (2000)) [7] describes that an open reading frame of unknown function Rv1695 from M. tuberculosis (Mycobacterium tuberculosis) of the genus Mycobacterium, H37Rv encodes a polyphosphate-dependent NAD+ kinase. However, optimal reaction conditions for preparing NADP have not been examined well, and development of processes for more efficiently and inexpensively preparing NADP have been demanded.